Safety and Efficacy Study of Idelalisib (GS-1101, CAL-101) in Patients With Previously Treated Low-grade Lymphoma

Sponsor
Gilead Sciences (Industry)
Overall Status
Completed
CT.gov ID
NCT01306643
Collaborator
(none)
18
2
1
53.9
9
0.2

Study Details

Study Description

Brief Summary

The primary objectives of this study is to evaluate the safety and efficacy of idelalisib (GS-1101, CAL-101) in participants with previously treated indolent non-Hodgkin lymphoma (iNHL).

Eligible patients will initiate oral therapy with idelalisib at a starting dose of 150 mg twice per day. Treatment with idelalisib can continue in compliant participants for up to twelve 28-day cycles of idelalisib. Participants who appear to be benefiting from treatment at the completion of 12 cycles of treatment with idelalisib may be eligible for participation in a long-term safety extension study of idelalisib.

Study Design

Study Type:
Interventional
Actual Enrollment :
18 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Single-agent Idelalisib for Previously Treated Low-grade Lymphoma: A Phase 1/2 Study of Safety, Efficacy, and Flow-cytometric Assessment of Tumor-cell Signaling Events
Study Start Date :
Feb 1, 2011
Actual Primary Completion Date :
Aug 1, 2015
Actual Study Completion Date :
Aug 1, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: Idelalisib

Drug: Idelalisib
Tablet(s) administered orally twice daily
Other Names:
  • GS-1101
  • CAL-101
  • Zydelig®
  • Outcome Measures

    Primary Outcome Measures

    1. Overall Safety of Idelalisib [30 days post last study treatment (up to 12 months)]

      The overall safety of idelalisib was assessed as the percentage of participants experiencing treatment-emergent adverse events (AEs; Serious AEs, Grade ≥ 3 AEs, AEs related to idelalisib, and AEs leading to discontinuation of idelalisib).

    2. Clinical Response: Overall Response Rate [Up to twelve 28-day cycles (maximum of 12 months)]

      Participants were assessed for clinical response by appropriate imaging at the end of cycles 3, 6, 9, and 12. Overall response rate (ORR) was assessed based on standardized criteria (Cheson 2007), and was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) based on investigator assessment after the start of idelalisib treatment until progression or the end of study drug treatment. CR was defined as the disappearance of all evidence of disease. PR was defined the regression of measurable disease and no new sites.

    Secondary Outcome Measures

    1. Flow Cytometric Measurement of Constitutive or Inducible Phosphorylation of Akt (at S473) and S6 Within Tumor B Cells [Up to twelve 28-day cycles (maximum of 12 months)]

    2. Flow Cytometric Measurement of Tumoral and Peripheral Blood T and NK Cells [Up to twelve 28-day cycles (maximum of 12 months)]

    3. Changes in Concentration of Peripheral Blood Chemokines and Cytokines [Up to twelve 28-day cycles (maximum of 12 months)]

    4. Changes in Liver Imaging as Assessed by Magnetic Resonance Imaging (MRI) and Gadoxetic Acid (GD-EOB-DTPA) Contrast [Up to twelve 28-day cycles (maximum of 12 months)]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Previously treated relapsed or refractory B-cell iNHL

    • Provide written informed consent

    Exclusion Criteria:
    • Pregnant or nursing

    • Active, serious infection requiring systemic therapy

    • Positive test for HIV antibodies

    • Active hepatitis B or C viral infection

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Stanford Cancer Center Palo Alto California United States 94304-5548
    2 Mount Sinai School of Medicine New York New York United States 10029

    Sponsors and Collaborators

    • Gilead Sciences

    Investigators

    • Study Director: Gilead Study Director, Gilead Sciences

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT01306643
    Other Study ID Numbers:
    • 101-10
    First Posted:
    Mar 2, 2011
    Last Update Posted:
    Nov 19, 2018
    Last Verified:
    Oct 1, 2016

    Study Results

    Participant Flow

    Recruitment Details Participants were enrolled at 2 study sites in the United States. The first participant was screened on 22 February 2011. The last study visit occurred on 24 August 2015.
    Pre-assignment Detail 24 participants were screened.
    Arm/Group Title Idelalisib
    Arm/Group Description Idelalisib 150 mg tablet(s) administered orally twice daily for a maximum of twelve 28-day cycles
    Period Title: Overall Study
    STARTED 18
    COMPLETED 5
    NOT COMPLETED 13

    Baseline Characteristics

    Arm/Group Title Idelalisib
    Arm/Group Description Idelalisib 150 mg tablet(s) administered orally twice daily for a maximum of twelve 28-day cycles
    Overall Participants 18
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    58
    (12.6)
    Sex: Female, Male (Count of Participants)
    Female
    8
    44.4%
    Male
    10
    55.6%
    Diagnosis (participants) [Number]
    Follicular lymphoma
    10
    55.6%
    Marginal zone lymphoma
    3
    16.7%
    Small lymphocytic lymphoma
    4
    22.2%
    Missing
    1
    5.6%

    Outcome Measures

    1. Primary Outcome
    Title Overall Safety of Idelalisib
    Description The overall safety of idelalisib was assessed as the percentage of participants experiencing treatment-emergent adverse events (AEs; Serious AEs, Grade ≥ 3 AEs, AEs related to idelalisib, and AEs leading to discontinuation of idelalisib).
    Time Frame 30 days post last study treatment (up to 12 months)

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) Analysis Set: all enrolled participants who received at least 1 dose of idelalisib.
    Arm/Group Title Idelalisib
    Arm/Group Description Idelalisib 150 mg tablet(s) administered orally twice daily for a maximum of twelve 28-day cycles
    Measure Participants 18
    Any AE
    88.9
    493.9%
    Serious AE
    27.8
    154.4%
    Grade ≥ 3 AE
    55.6
    308.9%
    AE related to idelalisib
    83.3
    462.8%
    AE leading to permanent drug discontinuation
    27.8
    154.4%
    2. Primary Outcome
    Title Clinical Response: Overall Response Rate
    Description Participants were assessed for clinical response by appropriate imaging at the end of cycles 3, 6, 9, and 12. Overall response rate (ORR) was assessed based on standardized criteria (Cheson 2007), and was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) based on investigator assessment after the start of idelalisib treatment until progression or the end of study drug treatment. CR was defined as the disappearance of all evidence of disease. PR was defined the regression of measurable disease and no new sites.
    Time Frame Up to twelve 28-day cycles (maximum of 12 months)

    Outcome Measure Data

    Analysis Population Description
    ITT Analysis Set
    Arm/Group Title Idelalisib
    Arm/Group Description Idelalisib 150 mg tablet(s) administered orally twice daily for a maximum of twelve 28-day cycles
    Measure Participants 18
    Number (95% Confidence Interval) [percentage of participants]
    44.4
    246.7%
    3. Secondary Outcome
    Title Flow Cytometric Measurement of Constitutive or Inducible Phosphorylation of Akt (at S473) and S6 Within Tumor B Cells
    Description
    Time Frame Up to twelve 28-day cycles (maximum of 12 months)

    Outcome Measure Data

    Analysis Population Description
    Data are not available because the samples and analysis results (performed at the sites) could not be retrieved by Gilead.
    Arm/Group Title Idelalisib
    Arm/Group Description Idelalisib 150 mg tablet(s) administered orally twice daily for a maximum of twelve 28-day cycles
    Measure Participants 0
    4. Secondary Outcome
    Title Flow Cytometric Measurement of Tumoral and Peripheral Blood T and NK Cells
    Description
    Time Frame Up to twelve 28-day cycles (maximum of 12 months)

    Outcome Measure Data

    Analysis Population Description
    Data are not available because the samples and analysis results (performed at the sites) could not be retrieved by Gilead.
    Arm/Group Title Idelalisib
    Arm/Group Description Idelalisib 150 mg tablet(s) administered orally twice daily for a maximum of twelve 28-day cycles
    Measure Participants 0
    5. Secondary Outcome
    Title Changes in Concentration of Peripheral Blood Chemokines and Cytokines
    Description
    Time Frame Up to twelve 28-day cycles (maximum of 12 months)

    Outcome Measure Data

    Analysis Population Description
    Data are not available because the samples and analysis results (performed at the sites) could not be retrieved by Gilead.
    Arm/Group Title Idelalisib
    Arm/Group Description Idelalisib 150 mg tablet(s) administered orally twice daily for a maximum of twelve 28-day cycles
    Measure Participants 0
    6. Secondary Outcome
    Title Changes in Liver Imaging as Assessed by Magnetic Resonance Imaging (MRI) and Gadoxetic Acid (GD-EOB-DTPA) Contrast
    Description
    Time Frame Up to twelve 28-day cycles (maximum of 12 months)

    Outcome Measure Data

    Analysis Population Description
    Data are not available because the samples and analysis results (performed at the sites) could not be retrieved by Gilead.
    Arm/Group Title Idelalisib
    Arm/Group Description Idelalisib 150 mg tablet(s) administered orally twice daily for a maximum of twelve 28-day cycles
    Measure Participants 0

    Adverse Events

    Time Frame 30 days post last study treatment (up to 12 months)
    Adverse Event Reporting Description ITT Analysis Set
    Arm/Group Title Idelalisib
    Arm/Group Description Idelalisib 150 mg tablet(s) administered orally twice daily for a maximum of twelve 28-day cycles
    All Cause Mortality
    Idelalisib
    Affected / at Risk (%) # Events
    Total / (NaN)
    Serious Adverse Events
    Idelalisib
    Affected / at Risk (%) # Events
    Total 5/18 (27.8%)
    Cardiac disorders
    Atrial fibrillation 1/18 (5.6%)
    Gastrointestinal disorders
    Gastrointestinal haemorrhage 1/18 (5.6%)
    Infections and infestations
    Cellulitis 1/18 (5.6%)
    Sepsis 1/18 (5.6%)
    Investigations
    Alanine aminotransferase increased 1/18 (5.6%)
    Aspartate aminotransferase increased 1/18 (5.6%)
    Transaminases increased 1/18 (5.6%)
    Metabolism and nutrition disorders
    Tumour lysis syndrome 2/18 (11.1%)
    Renal and urinary disorders
    Renal failure 2/18 (11.1%)
    Respiratory, thoracic and mediastinal disorders
    Hypoxia 1/18 (5.6%)
    Pneumonitis 1/18 (5.6%)
    Pneumothorax 1/18 (5.6%)
    Other (Not Including Serious) Adverse Events
    Idelalisib
    Affected / at Risk (%) # Events
    Total 15/18 (83.3%)
    Blood and lymphatic system disorders
    Neutropenia 3/18 (16.7%)
    Thrombocytopenia 2/18 (11.1%)
    Cardiac disorders
    Atrial fibrillation 1/18 (5.6%)
    Atrial tachycardia 1/18 (5.6%)
    Palpitations 1/18 (5.6%)
    Ear and labyrinth disorders
    Vertigo 2/18 (11.1%)
    Eye disorders
    Blepharospasm 1/18 (5.6%)
    Chalazion 1/18 (5.6%)
    Conjunctival hyperaemia 1/18 (5.6%)
    Keratitis 1/18 (5.6%)
    Photopsia 1/18 (5.6%)
    Vision blurred 1/18 (5.6%)
    Gastrointestinal disorders
    Abdominal discomfort 1/18 (5.6%)
    Abdominal pain 2/18 (11.1%)
    Colitis 1/18 (5.6%)
    Constipation 3/18 (16.7%)
    Diarrhoea 8/18 (44.4%)
    Flatulence 3/18 (16.7%)
    Gastrointestinal pain 1/18 (5.6%)
    Gastrooesophageal reflux disease 1/18 (5.6%)
    Haemorrhoidal haemorrhage 1/18 (5.6%)
    Lip discolouration 1/18 (5.6%)
    Nausea 7/18 (38.9%)
    Oral pain 1/18 (5.6%)
    Painful defaecation 1/18 (5.6%)
    Paraesthesia oral 1/18 (5.6%)
    Vomiting 5/18 (27.8%)
    General disorders
    Asthenia 2/18 (11.1%)
    Chest pain 1/18 (5.6%)
    Chills 2/18 (11.1%)
    Fatigue 8/18 (44.4%)
    Influenza like illness 2/18 (11.1%)
    Malaise 2/18 (11.1%)
    Pain 2/18 (11.1%)
    Pyrexia 5/18 (27.8%)
    Hepatobiliary disorders
    Hyperbilirubinaemia 1/18 (5.6%)
    Infections and infestations
    Atypical pneumonia 1/18 (5.6%)
    Candida infection 1/18 (5.6%)
    Conjunctivitis 1/18 (5.6%)
    Hordeolum 1/18 (5.6%)
    Nasopharyngitis 2/18 (11.1%)
    Upper respiratory tract infection 4/18 (22.2%)
    Injury, poisoning and procedural complications
    Contusion 2/18 (11.1%)
    Fall 1/18 (5.6%)
    Investigations
    Alanine aminotransferase increased 8/18 (44.4%)
    Aspartate aminotransferase increased 8/18 (44.4%)
    Blood bilirubin increased 2/18 (11.1%)
    Blood creatinine increased 1/18 (5.6%)
    Blood phosphorus increased 1/18 (5.6%)
    Blood uric acid increased 1/18 (5.6%)
    Glomerular filtration rate decreased 1/18 (5.6%)
    Hepatic enzyme increased 1/18 (5.6%)
    Neutrophil count decreased 1/18 (5.6%)
    Transaminases increased 4/18 (22.2%)
    Weight decreased 2/18 (11.1%)
    Metabolism and nutrition disorders
    Decreased appetite 3/18 (16.7%)
    Dehydration 1/18 (5.6%)
    Hyperuricaemia 1/18 (5.6%)
    Hypokalaemia 1/18 (5.6%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 2/18 (11.1%)
    Back pain 2/18 (11.1%)
    Flank pain 1/18 (5.6%)
    Haemarthrosis 1/18 (5.6%)
    Joint stiffness 1/18 (5.6%)
    Muscle spasms 2/18 (11.1%)
    Muscular weakness 1/18 (5.6%)
    Musculoskeletal pain 1/18 (5.6%)
    Pain in extremity 3/18 (16.7%)
    Nervous system disorders
    Dysgeusia 3/18 (16.7%)
    Headache 4/18 (22.2%)
    Hypersomnia 1/18 (5.6%)
    Lethargy 2/18 (11.1%)
    Mental impairment 1/18 (5.6%)
    Neuropathy peripheral 1/18 (5.6%)
    Sinus headache 1/18 (5.6%)
    Psychiatric disorders
    Agitation 2/18 (11.1%)
    Confusional state 1/18 (5.6%)
    Emotional disorder 1/18 (5.6%)
    Insomnia 5/18 (27.8%)
    Renal and urinary disorders
    Chromaturia 1/18 (5.6%)
    Dysuria 1/18 (5.6%)
    Nocturia 1/18 (5.6%)
    Pollakiuria 1/18 (5.6%)
    Renal failure 1/18 (5.6%)
    Respiratory, thoracic and mediastinal disorders
    Cough 4/18 (22.2%)
    Dysphonia 1/18 (5.6%)
    Dyspnoea 2/18 (11.1%)
    Hypopnoea 1/18 (5.6%)
    Nasal congestion 1/18 (5.6%)
    Oropharyngeal pain 1/18 (5.6%)
    Pneumonitis 2/18 (11.1%)
    Productive cough 1/18 (5.6%)
    Skin and subcutaneous tissue disorders
    Acne 1/18 (5.6%)
    Exfoliative rash 3/18 (16.7%)
    Hyperhidrosis 2/18 (11.1%)
    Hyperkeratosis 1/18 (5.6%)
    Pruritus 3/18 (16.7%)
    Rash 5/18 (27.8%)
    Skin fissures 1/18 (5.6%)
    Vascular disorders
    Hot flush 1/18 (5.6%)
    Hypotension 1/18 (5.6%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years

    Results Point of Contact

    Name/Title Clinical Trial Disclosures
    Organization Gilead Sciences
    Phone
    Email ClinicalTrialDisclosures@gilead.com
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT01306643
    Other Study ID Numbers:
    • 101-10
    First Posted:
    Mar 2, 2011
    Last Update Posted:
    Nov 19, 2018
    Last Verified:
    Oct 1, 2016